AB0499 STEP-DOWN APPROACH IN METHOTREXATE USE FOR THE TREATMENT OF RHEUMATOID ARTHRITIS (STEMETRA): A PILOT STUDY DEMONSTRATING EFFICACY AND SAFETY OF SHORT-TERM HIGH DOSE METHOTREXATE
Authors: M. Pendolino, T. Serban, D. Camellino, P. Diana, A. Giusti, G. Bianchi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Methotrexate (MTX) is the cornerstone of Rheumatoid Arthritis (RA) treatment, showing a suitable efficacy-safety profile, relatively low-cost, and versatile routes and dosage administration. However, there are no clear indications yet on the optimal use of MTX in RA, whereas existing recommendations disagree on relevant aspects (eg. route, starting and maximal dose, titration increase/decrease, and intervals to monitor toxicity) [1]. <h3>Objectives</h3> To evaluate the efficacy and the safety of a step-down strategy to use subcutaneous (sc) MTX in patients with RA. <h3>Methods</h3> STEMETRA is a 16-week open-label, monocentric, pilot study. The protocol treatment schedule consisted of the administration of MTX 50 mg sc/week for 4 consecutive weeks, followed by 25 mg/week for 4 weeks, and then 15 mg/week for 4 weeks. All patients received oral supplementation of folinic acid (leucovorin) 12 mg, 12 hours after the injection of MTX. <h3>Results</h3> Fifteen patients (10 females and 5 males; mean age, 60 years (±11)) diagnosed with RA according to 2010 ACR/EULAR classification criteria and naïve to any RA treatment were enrolled. One patient was lost to follow-up after week 12; 4 patients withdrew because of adverse events; therefore, 10 patients concluded the study. A total of 14 adverse events occurred in 7 patients; 7 were of mild entity and tolerated by patients, 3 solved, and 4 were persistent and lead to withdrawal of the drug (Table 1). Mean DAS28(CRP) at baseline was 5.6 (±1.4), whereas, at week 16, mean DAS28(CRP) was 1.6(±1). Most patients who concluded the study achieved ACR70 response and the state of remission (7 out of 10), whereas 3 still showed moderate disease activity. <h3>Conclusion</h3> In this study, step-down MTX approach was effective in inducing remission in most of the patients enrolled. According to data reported in other studies (2,3), one third of them showed adverse events leading to the withdrawal of the drug. On the contrary, different studies in which MTX was used as in current clinical practice (at lower dosages) showed lower efficacy: in the ORAL START study, ACR70 response was reached only in 12% of naïve patients 6 months after MTX monotherapy (4), whereas in the PREMIER study, 26% of patients receiving MTX monotherapy obtained ACR70 response after one year [5]. Thus, short-term higher dose MTX usage could be more effective in order to reach remission earlier. Nonetheless these results should be confirmed in larger populations of patients. In conclusion, this approach could be considered as a valid regimen for a more optimal use of MTX. <h3>References</h3> [1]Valerio V, Kwok M, Loewen H, et al. Clin Rheumatol. 2021 Apr;40(4):1259-1271. PMID: 32876784 [2]Due E, Blomberg M, Skov L, et al. Acta Derm Venereol. 2012 Jul;92(4):353-4. PMID: 22001863 [3]Bassel K. El-Zorkany, Sherif M. Gamal, et al. The Egypt Rheumatol Vol 35, Issue 2, 2013, Pages 53-57, https://doi.org/10.1016/j.ejr.2013.01.003 [4]Lee EB, Fleischmann R, Hall S, et al. N Engl J Med. 2014 Jun 19;370(25):2377-86. PMID: 24941177 [5]Breedveld FC, Weisman MH, Kavanaugh AF, et al. Arthritis Rheum. 2006 Jan;54(1):26-37. PMID: 16385520 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.